The purpose of this project is to investigate a novel completely bioresorbable integrated structural/delivery scaffold for controlled BMP2 delivery in cervical spine fusion. Over 230,000 cervical spine fusions were performed in the US alone in 2008, accounting for 41% of all spine fusions. Due to enhanced clinical outcomes in lumbar spine fusion while simultaneously eliminating the need for graft harvest, off label usage increased significantly in cervical spine fusion. However, severe adverse effects including death were associated with BMP2 usage in cervical spine fusion, prompting the FDA to warn against BMP2 use in cervical spine fusion, as reported by the New York Times and Wall Street Journal. It is widely hypothesized that these adverse effects are due to high BMP2 dosages, poor BMP2 retention and uncontrolled BMP2 release by the currently approved collagen sponge carrier that allows BMP2 diffusion into surrounding soft tissues, with associated increased vascular edema and ectopic bone formation. Our laboratory has developed technology integrating topology optimization, bioresorbable polymer solid free-form fabrication, BMP2 conjugation, and bioresorbable fixation to develop a new structural/delivery system for cervical spine fusion. We will engineer this new structural/delivery system and test the delivery of BMP2 in a large pre-clinical (pig) animal model of cervical spine fusion. We hypothesize that topology optimized integrated porous structural carriers with surface area and mechanical modulus close to vertebral trabecular bone and a permeability greater than 10-8 m4/Ns conjugated with lower than clinical dosages (0.5 mg) of BMP2 will provide superior fusion in terms of time to fusion, and fusion mass volume and stiffness compared to current clinical cervical cage designs delivering BMP2 via conjugation or FDA approved collagen sponge. We will test this hypothesis by comparing optimized and clinical cage designs alone, with conjugated BMP2 delivery and with collagen sponge delivery. These experimental groups will allow us to specifically test if the new system provides both better load carrying distribution as well as better controlled bone formation using a different BMP2 delivery method. Successful completion of this proposal will provide a new paradigm for bioresorbable fusion systems in the cervical spine, achieving spinal fusion with lower, safer, and less expensive doses of BMP2.